DYT4
MCID: DYS163
MIFTS: 33

Dystonia 4, Torsion, Autosomal Dominant (DYT4)

Categories: Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Dystonia 4, Torsion, Autosomal Dominant

MalaCards integrated aliases for Dystonia 4, Torsion, Autosomal Dominant:

Name: Dystonia 4, Torsion, Autosomal Dominant 56 73 71
Dyt4 56 52 58 73
Dystonia Musculorum Deformans 4 56 52 73
Hereditary Whispering Dysphonia 52 58 73
Autosomal Dominant Torsion Dystonia 4 29 6
Whispering Dysphonia, Hereditary 56 71
Dystonia, Type 4, Torsion, Autosomal Dominant 39
Autosomal Dominant Torsion Dystonia-4 52
Primary Dystonia, Dyt4 Type 58
Whispering Dysphonia 52
Dyt-Tubb4a 52
Dystonia-4 73

Characteristics:

Orphanet epidemiological data:

58
primary dystonia, dyt4 type
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Adult;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
onset between 13 to 37 years
favorable response to alcohol
one large family has been reported (last curated june 2013)


HPO:

31
dystonia 4, torsion, autosomal dominant:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

OMIM 56 128101
OMIM Phenotypic Series 56 PS128100
MeSH 43 D004422
ICD10 via Orphanet 33 G24.1
UMLS via Orphanet 72 C1851943 C1860315
Orphanet 58 ORPHA98805
MedGen 41 C1851943
UMLS 71 C1851943 C1860315

Summaries for Dystonia 4, Torsion, Autosomal Dominant

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 98805 Definition DYT4 type primary dystonia is characterized by predominantly laryngeal dystonia (manifesting as whispering dysphonia) and cervical dystonia (manifesting as torticollis). Epidemiology So far, the disease has been reported in one large Australian family. Clinical description The age of onset varies from 13 to 37 years. Some patients develop generalized dystonia and psychiatric symptoms. Etiology The locus for DYT4 remains unknown. Genetic counseling The disease is transmitted in an autosomal dominant manner. Visit the Orphanet disease page for more resources.

MalaCards based summary : Dystonia 4, Torsion, Autosomal Dominant, also known as dyt4, is related to dystonia and dystonia 1, torsion, autosomal dominant, and has symptoms including torticollis and dystonia, limb. An important gene associated with Dystonia 4, Torsion, Autosomal Dominant is TUBB4A (Tubulin Beta 4A Class IVa). Affiliated tissues include tongue and cerebellum, and related phenotypes are generalized dystonia and laryngeal dystonia

OMIM : 56 Dystonia-4, also known as whispering dysphonia, is an autosomal dominant neurologic disorder characterized by onset in the second to third decade of progressive laryngeal dysphonia followed by the involvement of other muscles, such as the neck or limbs. Some patients develop an ataxic gait (summary by Hersheson et al., 2013). (128101)

UniProtKB/Swiss-Prot : 73 Dystonia 4, torsion, autosomal dominant: A form of torsion dystonia, a disease defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. 'Torsion' refers to the twisting nature of body movements, often affecting the trunk. DYT4 is characterized by onset in the second to third decade of progressive laryngeal dysphonia followed by the involvement of other muscles, such as the neck or limbs. Some patients develop an ataxic gait.

Related Diseases for Dystonia 4, Torsion, Autosomal Dominant

Graphical network of the top 20 diseases related to Dystonia 4, Torsion, Autosomal Dominant:



Diseases related to Dystonia 4, Torsion, Autosomal Dominant

Symptoms & Phenotypes for Dystonia 4, Torsion, Autosomal Dominant

Human phenotypes related to Dystonia 4, Torsion, Autosomal Dominant:

58 31 (showing 22, show less)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 generalized dystonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0007325
2 laryngeal dystonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0012049
3 gait disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0001288
4 open mouth 58 31 frequent (33%) Frequent (79-30%) HP:0000194
5 torticollis 58 31 frequent (33%) Frequent (79-30%) HP:0000473
6 eunuchoid habitus 58 31 frequent (33%) Frequent (79-30%) HP:0003782
7 movement abnormality of the tongue 58 31 frequent (33%) Frequent (79-30%) HP:0000182
8 sunken cheeks 58 31 frequent (33%) Frequent (79-30%) HP:0009938
9 dysphagia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002015
10 respiratory distress 58 31 occasional (7.5%) Occasional (29-5%) HP:0002098
11 kyphoscoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002751
12 dementia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000726
13 dysdiadochokinesis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002075
14 blepharospasm 58 31 occasional (7.5%) Occasional (29-5%) HP:0000643
15 upper limb postural tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0007351
16 dysphonia 58 31 Very frequent (99-80%) HP:0001618
17 gait ataxia 31 HP:0002066
18 narrow face 31 HP:0000275
19 slender build 31 HP:0001533
20 involuntary movements 58 Occasional (29-5%)
21 torsion dystonia 31 HP:0001304
22 limb dystonia 31 HP:0002451

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
dysphonia
generalized dystonia
torsion dystonia
limb dystonia
abnormal 'hobby horse' ataxic gait

Head And Neck Neck:
torticollis

Head And Neck Face:
thin face
hollowed cheeks

Respiratory Larynx:
laryngeal adductor spasmodic dysphonia

Abdomen Gastrointestinal:
dysphagia

Growth Other:
thin body habitus

Head And Neck Mouth:
bradykinetic tongue

Voice:
whispering dysphonia

Clinical features from OMIM:

128101

UMLS symptoms related to Dystonia 4, Torsion, Autosomal Dominant:


torticollis, dystonia, limb

Drugs & Therapeutics for Dystonia 4, Torsion, Autosomal Dominant

Interventional clinical trials:

(showing 1, show less)
# Name Status NCT ID Phase Drugs
1 Dystonia Genotype-Phenotype Correlation: A Study to Identify Additional Genetic Associations That Contribute to Specific Dystonic Phenotypes Recruiting NCT03428009

Search NIH Clinical Center for Dystonia 4, Torsion, Autosomal Dominant

Genetic Tests for Dystonia 4, Torsion, Autosomal Dominant

Genetic tests related to Dystonia 4, Torsion, Autosomal Dominant:

# Genetic test Affiliating Genes
1 Autosomal Dominant Torsion Dystonia 4 29 TUBB4A

Anatomical Context for Dystonia 4, Torsion, Autosomal Dominant

MalaCards organs/tissues related to Dystonia 4, Torsion, Autosomal Dominant:

40
Tongue, Cerebellum

Publications for Dystonia 4, Torsion, Autosomal Dominant

Articles related to Dystonia 4, Torsion, Autosomal Dominant:

(showing 30, show less)
# Title Authors PMID Year
1
Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene. 61 56 6
23595291 2013
2
Mutations in the autoregulatory domain of β-tubulin 4a cause hereditary dystonia. 61 56 6
23424103 2013
3
Autoregulated instability of beta-tubulin mRNAs by recognition of the nascent amino terminus of beta-tubulin. 56 6
3405308 1988
4
Hereditary whispering dysphonia. 56 6
3156966 1985
5
Whispering dysphonia in an Australian family (DYT4): a clinical and genetic reappraisal. 61 56
21956287 2011
6
Hereditary Dystonia Overview 6
20301334 2003
7
Primary torsion dystonia: the search for genes is not over. 56
10449567 1999
8
Evidence for locus heterogeneity in autosomal dominant torsion dystonia. 56
8432555 1993
9
Dystonia-4 (DYT4)-associated TUBB4A mutants exhibit disorganized microtubule networks and inhibit neuronal process growth. 61
29127012 2018
10
Phenomenology, genetics, and CNS network abnormalities in laryngeal dystonia: A 30-year experience. 61
29219190 2018
11
TUBB4A mutations result in specific neuronal and oligodendrocytic defects that closely match clinically distinct phenotypes. 61
28973395 2017
12
Screening study of TUBB4A in isolated dystonia. 61
28655586 2017
13
A novel TUBB4A mutation G96R identified in a patient with hypomyelinating leukodystrophy onset beyond adolescence. 61
28791129 2017
14
Dystonia-Causing Mutations as a Contribution to the Etiology of Spasmodic Dysphonia. 61
27188707 2016
15
GNAL mutation in isolated laryngeal dystonia. 61
27093447 2016
16
Large-scale TUBB4A mutational screening in isolated dystonia and controls. 61
26318963 2015
17
H-ABC syndrome and DYT4: Variable expressivity or pleiotropy of TUBB4 mutations? 61
25545912 2015
18
Recent advances in the genetics of dystonia. 61
24952478 2014
19
Expansion of the spectrum of TUBB4A-related disorders: a new phenotype associated with a novel mutation in the TUBB4A gene. 61
24526230 2014
20
Pathogenic variants in TUBB4A are not found in primary dystonia. 61
24598712 2014
21
A direct interaction between leucine-rich repeat kinase 2 and specific β-tubulin isoforms regulates tubulin acetylation. 61
24275654 2014
22
Genetics in dystonia. 61
24262166 2014
23
Dystonia. 61
24092288 2013
24
De Novo mutations in the β-tubulin gene TUBB4: from DYT4 to leukoencephalopathy with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC syndrome). 61
24013879 2013
25
Genetics of dystonia: what's known? What's new? What's next? 61
23893446 2013
26
Genetic issues in the diagnosis of dystonias. 61
23596437 2013
27
[Genetics of dystonia]. 61
19685389 2009
28
Mutations in THAP1 (DYT6) and generalised dystonia with prominent spasmodic dysphonia: a genetic screening study. 61
19345148 2009
29
[Genetics of dystonia]. 61
10919137 2000
30
Genetics of primary dystonia. 61
12194383 1999

Variations for Dystonia 4, Torsion, Autosomal Dominant

ClinVar genetic disease variations for Dystonia 4, Torsion, Autosomal Dominant:

6 (showing 5, show less) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TUBB4A NM_006087.4(TUBB4A):c.4C>G (p.Arg2Gly)SNV Pathogenic 50984 rs587776983 19:6502220-6502220 19:6502209-6502209
2 TUBB4A NM_006087.4(TUBB4A):c.811G>A (p.Ala271Thr)SNV Pathogenic 92111 rs587777074 19:6495699-6495699 19:6495688-6495688
3 TUBB4A NM_006087.4(TUBB4A):c.1228G>A (p.Glu410Lys)SNV Pathogenic 135658 rs587777428 19:6495282-6495282 19:6495271-6495271
4 TUBB4A NM_006087.4(TUBB4A):c.1181T>C (p.Phe394Ser)SNV Likely pathogenic 689794 19:6495329-6495329 19:6495318-6495318
5 TUBB4A NM_006087.4(TUBB4A):c.238C>T (p.Pro80Ser)SNV Benign 692150 19:6501337-6501337 19:6501326-6501326

UniProtKB/Swiss-Prot genetic disease variations for Dystonia 4, Torsion, Autosomal Dominant:

73 (showing 1, show less)
# Symbol AA change Variation ID SNP ID
1 TUBB4A p.Arg2Gly VAR_069798 rs587776983

Expression for Dystonia 4, Torsion, Autosomal Dominant

Search GEO for disease gene expression data for Dystonia 4, Torsion, Autosomal Dominant.

Pathways for Dystonia 4, Torsion, Autosomal Dominant

GO Terms for Dystonia 4, Torsion, Autosomal Dominant

Sources for Dystonia 4, Torsion, Autosomal Dominant

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